Sodium Carbonate → 2-Chloro-4-methyl-6-(4-trifluoromethyl-phenyl)-pyrimidine

HRID 626883Notes

Reaction equation

HRID 626883 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4]([CH3:9])[N:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[F:16][C:17]([F:28])([F:27])[C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1>COCCOC.O.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[N:3]=[C:4]([CH3:9])[CH:5]=[C:6]([C:21]2[CH:22]=[CH:23][C:18]([C:17]([F:28])([F:27])[F:16])=[CH:19][CH:20]=2)[N:7]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 794712,4-Dichloro-6-methylpyrimidineHCID 27343894-(Trifluoromethyl)phenylboronic acid

Product 1

HCID 574686142-Chloro-4-methyl-6-(4-trifluoromethyl-phenyl)-pyrimidineYield 58.5%

Reagents, catalysts & solvents 3

HCID 178419050HCID 178419050, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 2,4-dichloro-6-methyl-pyrimidine (5 g, 30.67 mmol) in 1,2-dimethoxyethane (35 mL) and water (25 mL) was added sodium carbonate (9.75 g, 92.03 mmol), and 4-(trifluoromethyl)-phenylboronic acid (5.53 g, 29.14 mmol). This was degassed with nitrogen for 5 minutes. The bis(triphenylphosphine)palladium (II) dichloride (1.08 g, 1.53 mmol) was then added and the reaction was heated to 90° C. overnight. The solvent was evaporated and the residue was partitioned between water (300 mL) and EtOAc (300 mL). The organics were washed with brine (100 mL), dried over MgSO4 and concentrated in vacuo to afford a yellow oil. The material was purified using a Biotage SP4, 0 to 50% i-hexane/EtOAc and the fractions containing the lower (major) spot were collected and the solvent evaporated to afford the 2-chloro-4-methyl-6-[4-(trifluoromethyl)-phenyl]pyrimidine (D11) (4.65 g, 17.06 mmol, 55.6% yield) as a colourless solid.

Workup

  1. customThis was degassed with nitrogen for 5 minutes
  2. customThe solvent was evaporated
  3. customthe residue was partitioned between water (300 mL) and EtOAc (300 mL)
  4. washThe organics were washed with brine (100 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customto afford a yellow oil
  8. customThe material was purified
  9. additionthe fractions containing the lower (major) spot
  10. customwere collected
  11. customthe solvent evaporated

Sources & evidence

ORD record
ord-14d8386c4cd245f3833c2c5e10b4d6c1
Source dataset
uspto-grants-2016_04
Patent number
US09309254B2

Reaction notes

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